Background: Bone morphogenetic proteins are a family of cytokines and growth factors that are involved in tumorigenesis. ZCCHC12 (SIZN1), as a transcriptional coactivator of bone morphogenetic protein signaling, is identified as a positive regulator of central nervous system development during embryogenesis. It positively regulates the CREB and AP1 transcription factors that cooperate with the bone morphogenetic protein signaling pathway. In the present study, SIZN1 mRNA expression was assessed in esophageal squamous cell carcinoma patients.Methods: The levels of SIZN1 mRNA expression in tumor tissues from 50 patients with esophageal squamous cell carcinoma were compared with their corresponding normal margins by using real-time polymerase chain reaction.Results: We observed that 10 out of 50 (20%) cases overexpressed SIZN1, whereas 40 out of 50 (80%) cases showed either normal or under expression of SIZN1. There was a significant correlation between the levels of SIZN1 mRNA expression and tumor depth of invasion (P=0.040). Furthermore, a significant correlation between lymph node metastasis and SIZN1 mRNA expression was observed in esophageal squamous cell carcinoma patients (P=0.036).Conclusion: This study is the first report that has assessed SIZN1 expression in esophageal squamous cell carcinoma patients. SIZN1 can be a potential therapeutic target for primary esophageal squamous cell carcinoma because of its role in the early stages of tumor progression and metastasis.